Bio-Micro-Systems for Diagnostic Applications, Disease Prevention and Creating Tools for Biological Research

This thesis, divided into two parts, describes the development of 5 novel Bio-Micro-System devices. The term Bio-Micro-System has been used here to describe BioMEMS and 3D printed devices, with the dimensions of key components ranging from micrometers to a millimeter. Part A is focused on ‘Medical’ Micro-System devices that can potentially solve common medical problems. Part B is focused on ‘Biological’ Micro-System devices/tools for facilitating/enabling biological research. Specifically, Part A describes two implantable, electronics-free intraocular pressure (IOP) microsensors for the medical management of glaucoma: 1) Near Infrared Fluorescence-based Optomechanical (NiFO) technology - Consists of an implantable, pressure sensor that ‘optically encodes’ pressure in the near infrared (NIR) regime. A non-implantable, portable and compact optical head is used to excite the sensor and collect the emitted NIR light. The thesis discusses optimized device architecture and microfabrication approaches for best performance commercialization. 2) Displacement based Contrast Imaging (DCI) technology - A proof of concept, fluid pressure sensing scheme is shown to operate over a pressure range of 0–100 mbar (∼2 mbar resolution between 0–20 mbar,∼10 mbar resolution between 20–100 mbar), with a maximum error of <7% throughout its dynamic range. The thesis introduces the DCI technology and discusses its application as an IOP sensor. Moreover, Part A also describes a Touch-activated Sanitizer Dispensing (TSD) system for combating community acquired infections. The TSD can be mounted on any surface that is exposed to high human traffic and consists of an array of human-powered, miniaturized valves that deliver a small amount of disinfectant when touch actuated. The device disinfects the person’s hand that is touching it while being self-sterilized at the same time. The thesis describes the design and implementation of a proof of concept TSD that can disinfect an area equivalent to the size of a thumb. A significant (~ 10 fold) reduction in microbiological load is demonstrated on the fingertip and device surface within the first 24 hours. The size and footprint of the TSD can be scaled up as needed to improve hand hygiene compliance. In Part B, we developed a microfluidic chip for immobilizing Drosophila melanogaster larva by creating a cold micro-environment around the larva. After characterizing on chip temperature distribution and larval body movement, results indicate that the method is appropriate for repetitive and reversible, short-term (several minutes) immobilization. The method offers the added advantage of using the same chip to accommodate and immobilize larvae across all developmental stages (1st instar-late 3rd instar). Besides the demonstrated applications of the chip in high resolution observation of sub cellular events such as mitochondrial trafficking in neurons and neuro-synaptic growth, we envision the use of this method in a wide variety of biological imaging studies employing the Drosophila larval system, including cellular development and other studies. Finally, Part B also describes a 3D printed millifluidic device for CO2 immobilization of Caenorhabditis elegans populations. We developed a novel 3D printed device for immobilizing populations of Caenorhabditis elegans by creating a localized CO2 environment while the animals are maintained on the surface of agar. The results indicate that the method is easy to implement, is appropriate for short-term (20 minutes) immobilization and allows recovery within a few minutes. We envision its use in a wide variety of biological studies in Caenorhabditis elegan, including cellular development and neuronal regeneration studies.PHDBiomedical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/144050/1/amritarc_1.pd